Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway

Gurusamy, N. and Lekli, I. and Mukherjee, S. and Ray, D. and Ahsan, Md. K. and Gherghiceanu, M. and Popescu, L. M. and Das, D. K. (2010) Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovascular Research, 86 (1). pp. 103-112. ISSN 0008-6363

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Official URL: http://dx.doi.org/10.1093/cvr/cvp384

Abstract

AIMS: On the basis of our previous reports that cardioprotection induced by ischaemic preconditioning induces autophagy and that resveratrol, a polyphenolic antioxidant present in grapes and red wine induces preconditioning-like effects, we sought to determine if resveratrol could induce autophagy. METHODS AND RESULTS: Resveratrol at lower doses (0.1 and 1 microM in H9c2 cardiac myoblast cells and 2.5 mg/kg/day in rats) induced cardiac autophagy shown by enhanced formation of autophagosomes and its component LC3-II after hypoxia-reoxygenation or ischaemia-reperfusion. The autophagy was attenuated with the higher dose of resveratrol. The induction of autophagy was correlated with enhanced cell survival and decreased apoptosis. Treatment with rapamycin (100 nM), a known inducer of autophagy, did not further increase autophagy compared with resveratrol alone. Autophagic inhibitors, wortmannin (2 microM) and 3-methyladenine (10 mM), significantly attenuated the resveratrol-induced autophagy and induced cell death. The activation of mammalian target of rapamycin (mTOR) was differentially regulated by low-dose resveratrol, i.e. the phosphorylation of mTOR at serine 2448 was inhibited, whereas the phosphorylation of mTOR at serine 2481 was increased, which was attenuated with a higher dose of resveratrol. Although resveratrol attenuated the activation of mTOR complex 1, low-dose resveratrol significantly induced the expression of Rictor, a component of mTOR complex 2, and activated its downstream survival kinase Akt (Ser 473). Resveratrol-induced Rictor was found to bind with mTOR. Furthermore, treatment with Rictor siRNA attenuated the resveratrol-induced autophagy.

Item Type: Article
Subjects: Pharmaceutical Sciences
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: NARASIMMAN GURUSAMY
Date Deposited: 01 May 2017 09:39
Last Modified: 01 May 2017 09:39
URI: http://eprints.kku.edu.sa/id/eprint/831

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